Regensburg, 1st June 2011. Antisense Pharma GmbH, a biopharmaceutical company headquartered in Germany, has announced the granting
of patents for an application system, which for the rst time allows long-term and outpatient administration of therapeutic substances into brain
tissue using the so-called Convection Enhanced Delivery (CED). The portable system has been specially developed for the treatment of brain
tumor patients using Antisense Pharma‘s innovative drug trabedersen. Patents currently granted cover Europe, the USA, Canada, Japan and India,
with more patents in other countries being led.
The two sides of the blood-brain barrier –
causing 98% of potential neurotherapeutics to fail
There is a physiological diffusion barrier, which controls the exchange
of substances between the circulating blood and the brain in order to
protect the sensitive brain, ensuring a stable environment in the brain
tissue. High molecular, charged or polar substances require speci c
transport systems in order to reach the brain – an effective protection,
which however means that the blood-brain barrier blocks about
98% of potential neurotherapeutics.1 “The dif culty of administering
a therapeutic dose of a pharmacologically effective substance into
the brain tissue is one of the main reasons for the currently very
few therapy options we can offer to brain tumor patients “, says
Dr. Karl-Hermann Schlingensiepen, Chief Executive Of cer of Antisense
Pharma. “There is only a very small number of substances capable to
pass the blood-brain barrier so that they can be administered orally or
by means of intravenous infusion“.
Convection Enhanced Delivery (CED) for optimum
penetration of tissue
While an (intraventricular or intrathecal) injection or the placement
of a drug carrier in the brain tissue circumvents the blood-brain
barrier, however the regional diffusion of the drug is very limited.
The concentration of the administered substance is therefore high in
the direct vicinity of the place of injection, but it rapidly decreases
with increasing distance. In contrast, the new application system by
Antisense Pharma uses a special infusion technology. Convection
Enhanced Delivery (CED) provides a high and uniform concentration
of active substances in the brain tissue – even at a distance from
the place of infusion. The substance is administered directly into the
tumor or the surrounding brain tissue using a permanent, pressuresupported
infusion using a special catheter/pump system. Since CED
builds up a pressure gradient, a clearly higher and more homogeneous
penetration volume can be achieved compared to conventional
diffusion. The substance penetration depends on the tissue density,
Intracranial use of CED – a high-precision technology
Originally developed at the National Institutes for Health (USA), the
potential of the CED technology has now been documented by
numerous animal studies, clinical studies and state-of-the-art imaging
systems.3,4,5,6 This technology offers new application options for new
and also for already approved substances – but its clinical use requires
a suitable application system: “A CED-based intracranial infusion is a
challenge for the pump technology used. Our brain is enclosed by
solid cranial bones. The available space tolerates only minor infusion
volumes which have to be infused smoothly using a constant pressure“,
Dr. Hubert Heinrichs, Chief Medical Of cer at Antisense Pharma
explains. This mode of administration has so far required the use of
stationary application systems and the patients had to be hospitalized
for the complete therapy, involving an increased risk of infection . With
the development of the rst portable, now patented CED application
system, the German entrepreneurs are cutting edge: “The option of a
CED-based treatment using a portable application system over weeks
and months could well stimulate the development of urgently required neurotherapeutics“, Dr. Heinrichs takes a look ahead.
Antisense Pharma develops rst portable CED application
system for the ambulant intracranial administration of
neurotherapeutics
Trabedersen, the drug developed by Antisense Pharma to combat
malignant brain tumors, is also not able to pass the blood-brain barrier.
“Earlier examinations of brain tumor cells had already shown the
very high ef cacy of trabedersen“, Dr. Schlingensiepen remembers.
“Due to the molecular structure, it was obvious that we would have
to administer the substance directly into the brain for an extensive
period of time. It is Antisense Pharma’s declared philosophy to allow
critically ill people not only a longer life expectancy, but also a clearly
improved quality of life. We have therefore developed in parallel to the
compound also a very patient-friendly application system“.
The infusion system which has now been patented consists of
carefully harmonized components: after the catheter has been
stereotactically placed in the tumor, the drug is administered via an
infusion line using an external, programmable, portable pump. The
implantation of the catheter is a neurosurgical intervention, which is
geared to the placement of a shunt for hydrocephalus patients where
excessive brain liquid is diverted into the blood circulation. “The new
application system uses the innovative approach so that a known and
secure technology is used successfully in a completely new clinical
context“, Dr. Heinrichs explains. The brain catheter is inserted through
the skin to a port chamber which is usually placed in the chest muscle.
The chamber is then connected to an external infusion line, which in
turn is connected to a small, portable infusion pump that can easily be
attached to the belt.
“Using this application system, we are able to administer highly
effective drugs, by-passing the blood-brain barrier. At the same
time, we allow patients to continue living their normal lives during the
therapy: once the catheter system has been positioned, no extensive
hospitalization is required. The total 5-month treatment using
trabedersen provides patients with maximum mobility and quality of
life“, Dr. Schlingensiepen summarizes.
About Antisense Pharma GmbH
Antisense Pharma is a biopharmaceutical company located in
Regensburg, Germany. The company focuses on targeted therapies for
malignant tumors and is dedicated to discovering and developing drugs
based on antisense technology for worldwide commercialization. The
medications speci cally block the synthesis of key cancer proteins.
Antisense Pharma has clinical trials running that involve patients with
brain tumors, advanced pancreatic carcinoma, malignant melanoma
and colorectal carcinoma. Therapies for other indications are under
preclinical development. The company has been honored with the
German Founder‘s Award and the Bavarian Innovation Award and
received the Innovation Prize TOP 100.
